Mutant-bearing stocks of rabbits are valuable models of human constitutional diseases. We propose to investigate one such model in depth. Buphthalmia (bu/bu) in the rabbit is similar to human congenital glaucoma. The numerous effects of the bu gene have considerable similarity to the pathological conditions associated with Vitamin A deficiency. Therefore, we will analyze the long-term effects of Vitamin A and its precursor, beta-carotene, on the genetic penetrance and expressivity of the bu gene, in order to determine a therapeutic regimen for preventing its consequences. Glaucomatous lesions have been observed by histological techniques at birth. Therefore, we will investigate the prenatal development of glaucoma in the rabbit under standard nutritional conditions to ascertain at what point and how the disease first becomes manifest. Recent analyses of serum and aqueous humor revealed marked reductions in aqueous humor ascorbate levels associated with progressive stages of glaucoma. Also, administration of ascorbate intravenously lowered the intraocular pressure of both normal and glaucomatous rabbits. Therefore, it seems necessary to analyze both serum and aqueous humor for other biochemical variants in order to determine the complete etiology of the disease.